RFA using the Barrx™ Ablation System (Covidien, Sunnyvale, CA) has been most commonly used as ablation therapy, since the multicenter, randomized, sham-controlled trial involving 127 patients with Barrett’s esophagus demonstrated that 81 % of patients with HGD had complete eradication of dysplasia with RFA compared to 19 % in the control group (no RFA) (p <0.001) and patients who underwent RFA had significantly less disease progression and fewer cancers developed during the follow-up of 12 months [35]. Either an ablation balloon catheter (Barrx™ 360 RFA Balloon Catheter) for circumferential ablation or an endoscopic mounted device (Barrx™ 90, 60, Ultra Long RFA Focal Catheter) for focal ablation can be selected based on the length, extension, and location of disease (Fig. 2.1). This system delivers a high-power, ultrashort burst of ablative energy to the abnormal esophageal epithelium, and the delivered energy provides uniform treatment to a depth of approximately 500 μm. Therefore, the depth of treatment is limited to the mucosal layer, thereby significantly reducing the risk of stricture formation. The rate of stricture formation was reported to be 6 % [35]. A further follow-up study demonstrated that patients’ quality of life significantly improved after the RFA treatment, although most patients were worried about esophageal cancer and esophagectomy before the RFA treatment [36]. Due to the limited depth of treatment, RFA is not indicated for invasive cancer.

Cryotherapy involves the topical application by spraying aerosolized liquid nitrogen or carbon dioxide onto the abnormal esophageal epithelium, providing intracellular disruption and ischemia while preserving the extracellular matrix and thereby minimizing fibrosis. A prospective study involving 98 patients with HGD has demonstrated that 97 % had complete eradication of HGD with no esophageal perforation [28]. Current cryotherapy devices require a venting system such as a nasogastric tube to help excessive nitrogen gas escape out of the esophagus and stomach, thus preventing perforation of the gastrointestinal tract. Furthermore, cryotherapy is associated with several issues including its nonuniform application using a handheld catheter, the fogging of scope lens, and the prolonged duration of the therapy. Currently, a novel through-the-scope cryoballoon device, which does not require a venting system and potentially delivers a uniform and reproducible ablation, has been under investigation, and further study to evaluate the safety and efficacy of this device is awaited.

EMR has been commonly used as both a diagnostic and therapeutic tool. There are primarily two techniques: cap resection technique and ligate-and-cut technique (Fig. 2.2) [39]. A randomized trial comparing these two techniques has demonstrated no difference in safety and efficacy between the techniques [40]. Both techniques are initiated by injecting normal saline into the submucosal space to lift the lesions away from the muscularis propria. The injection needle should be inserted into a submucosal space at the sharp angle to avoid transmural penetration of the needle. Injected saline acts as a “safety cushion” between the mucosa and muscularis propria to reduce the risk of unexpected complications such as perforation during the procedure. Additional injection of saline is sometimes required because the injected saline disappears within a few minutes. Difficulty lifting up the lesion by submucosal injection suggests invasion into the muscularis propria. For the cap resection technique, a clear plastic cap (either straight or oblique shaped) is attached to the tip of endoscope. The oblique-shaped caps are usually used for esophageal lesions, while the straight caps are most commonly used for the lesions in the stomach and colon. The mucosal-submucosal complex is then sucked into a cap mounted on an endoscope, creating a pseudopolyp. The pseudopolyp is then resected by being captured at its base with a cautery snare which is positioned inside the cap [41]. For the ligate-and-cut technique, the only difference to the cap technique is to deploy a band to create a pseudopolyp [26, 27]. Currently, there is a novel multiband mucosectomy device available, which uses a specially designed multiple-band ligator and allows endoscopists to perform ligation and subsequent immediate resection without removal of the endoscope by passing a cautery snare through the ligator handle. The retrieved specimen is pinned to a piece of cork and placed into preservative solution prior to processing for histological assessment. EMR is indicated for lesions less than 2 cm in diameter. Although en-bloc resection is ideal in any situation, piecemeal resection of large lesions (>2 cm) is acceptable; however, several studies have shown that piecemeal EMR is associated with incomplete resection and compromised histological assessment, likely causing the development of metachronous lesions [42, 43].

An early retrospective study from a single institution demonstrated that 98 % of patients with HGD and T1a adenocarcinoma (n = 115) achieved complete response to EMR; however, 30 % of patients developed metachronous cancers during a mean follow-up of 34 months [42]. In a further study from the same institution, several factors including piecemeal resection, long-segment BE, no ablation therapy of BE after a complete response, multifocal neoplasia, and time until complete response >10 months were found to be associated with frequent tumor recurrence after endoscopic resection (Table 2.3) [43]. Based on these results, combination therapy involving focal EMR to resect nodules followed by RFA to treat any residual flat Barrett’s epithelium has been investigated to minimize the development of recurrent disease. A recent multicenter, prospective study to evaluate the efficacy of this combination therapy has demonstrated that 95 % of patients with HGD or T1a adenocarcinoma (n = 24) had a complete response to the combination therapy and no recurrence occurred during a median follow-up of 22 months [44]. These studies emphasize the importance of intensive surveillance, the risk of metachronous lesions after endoscopic resection, the need for post-intervention intensive surveillance, and the necessity of discussing the possibility of recurrent cancers with patients prior to the initiation of endoscopic interventions.

ESD has been established as an advanced endoscopic resection technique to accomplish en bloc resection of lesions larger than 2 cm in diameter. ESD is expected to provide more accurate histological assessment for the lateral and deep margins of lesions and thus prevent or minimize the development of metachronous lesions. ESD employs the same concept of EMR but requires some modifications for en bloc resection of a large lesion. Each step is summarized in Fig. 2.3. ESD is initiated by a mucosal marking around the lesion by using electrocautery, thus easily identifying the location of the entire lesion after the submucosal injection (Fig. 2.4a). Subsequently, a solution is injected into the submucosal space to lift the lesion away from the muscularis propria. The injection solutions for ESD include normal saline, glycerol, and sodium hyaluronate. Sodium hyaluronate stays longer in the submucosal space than normal saline or glycerol and may be ideal for ESD. Diluted sodium hyaluronate (approximately 0.5 % solution) is usually mixed with epinephrine (0.01 mg/ml) and indigo carmine (0.04 mg/ml). The mucosal cutting is then performed to create the entry to the submucosal space by using a specialized endoscopic electocautery called “needle knife” (Fig. 2.4b, c). Several types of needle knives having different shaped tips are available, depending on the preference of endoscopists (Fig. 2.5). Once the submucosal space is entered, tension and counter-tension are maintained by a cap mounted on the tip of endoscope, which is placed in the plane between the mucosal-submucosal complex and the muscularis propria. The needle knife is then introduced through the endoscopic working channel, and the attachments and bridging vessels between the two layers are dissected. At the completion of this procedure, the lesion can be resected en bloc regardless of its size and the remaining thin layer of sm3 can be seen over the resected area (Fig. 2.4d). It is important to maintain this thin layer of sm3, especially when repair of a perforation is required. ESD is a “one-person” procedure and does not allow for assistant hands. It is therefore important to maintain adequate counter-traction on the mucosa to be resected throughout the procedure. For this purpose, it may be better to start with a partial mucosal incision rather than a circumferential mucosal incision, maintaining the continuity of the lesion to the esophageal epithelium as “counter-traction,” and mucosal incision and submucosal dissection should be repeated step by step. The advantage of gravity should be considered; submucosal dissection should be started from the upper portion of the lesion so that the dissected mucosa is pulled down by gravity, spontaneously exposing the submucosal layer. It is also worth considering repositioning patients to obtain the advantage of gravity.